Belimumab for Low Lymphocyte Count

Overseen By Irini Sereti, M.D.

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

Must not be taking: Glucocorticosteroids, Chemotherapy, Immunomodulants, others

Disqualifiers: HIV, Hepatitis, Tuberculosis, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 13

Duration: 24 weeks

20 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether belimumab, a drug, is safe for individuals with Idiopathic CD4 lymphopenia (ICL), a condition characterized by a low count of CD4 white blood cells that fight infections. Low CD4 levels can lead to more frequent illnesses, so researchers hope belimumab might provide some benefit. The study seeks participants diagnosed with ICL who are already part of another related study. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this potentially beneficial treatment.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are currently using systemic glucocorticosteroids or have used certain treatments like chemotherapy or immunomodulants in the past 6 months. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that belimumab is likely to be safe for humans?

Research has shown that belimumab is well-tolerated by people with systemic lupus erythematosus (SLE), an autoimmune disease. In these studies, patients taking belimumab experienced a decrease in certain immune cells without a significant drop in CD4 cells, which are crucial white blood cells that help fight infections. Additionally, belimumab has been used safely for up to seven years in patients with active SLE, demonstrating a strong safety record over time.

While these results are encouraging, it's important to understand that this trial is in an early stage. Although past research indicates belimumab appears safe, the current trial specifically examines its safety for people with Idiopathic CD4 lymphopenia (ICL). Therefore, safety is still being carefully monitored in this new context. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Belimumab is unique because it specifically targets and inhibits the activity of a protein called BAFF (B-cell activating factor), which plays a crucial role in the survival and proliferation of B lymphocytes. Unlike standard treatments for low lymphocyte count, which may not directly target the underlying mechanisms of the condition, Belimumab's targeted approach offers the potential for improved efficacy by directly addressing the imbalance in the immune system. Researchers are excited about this treatment because it promises a more precise intervention with potentially fewer side effects, as it hones in on a specific pathway involved in the disease process.

What evidence suggests that belimumab might be an effective treatment for low lymphocyte count?

Research has shown that belimumab can reduce symptoms in diseases like systemic lupus erythematosus (SLE) by controlling flare-ups, which are periods when symptoms worsen. Some studies found that belimumab significantly lowered the risk of these flare-ups. It also shows potential in treating other conditions related to issues with certain white blood cells, suggesting it might help with conditions like idiopathic CD4 lymphopenia (ICL). Although direct evidence for ICL is not yet available, belimumab's success in managing immune system-related diseases makes it a promising option for individuals with low CD4 counts. Participants in this trial will receive belimumab in a single-arm, open-label study to evaluate its effects on low lymphocyte count. ^{6 7 8 9 10}

Who Is on the Research Team?

Irini Sereti, M.D.

Principal Investigator

National Institute of Allergy and Infectious Diseases (NIAID)

Are You a Good Fit for This Trial?

Adults aged 18-70 with Idiopathic CD4 Lymphopenia (ICL), enrolled in NIH study 09-I-0102, and have low CD4 counts plus autoantibodies. They must use effective contraception and not be pregnant or breastfeeding. Exclusions include prior belimumab use, HIV, severe illnesses, certain infections, liver/kidney issues, recent vaccines, steroid use (except nasal/inhaler), cancer treatments within 6 months.

Inclusion Criteria

You must use birth control methods such as the pill, condoms, diaphragm, or an IUD to prevent pregnancy during the study.

My tests show positive for autoimmune antibodies.

Enrolled in study 09-I-0102

Exclusion Criteria

Pregnant

Hemoglobin < 8 g/dL

Serum creatinine > 1.5 times the upper limit of normal (ULN)

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Baseline

Baseline visit including repeats of screening tests and possible leukapheresis

1 day

1 visit (in-person)

Treatment

Participants receive 8 doses of belimumab through IV over 6 months

24 weeks

8 visits (in-person)

Follow-up

Participants have 3 follow-up visits at around 8, 16, and 24 weeks after the last dose

24 weeks

3 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Belimumab

Trial Overview The trial is testing the safety of a drug called belimumab for people with ICL. Participants will receive eight doses via IV over several weeks and undergo monitoring through physical exams as well as blood and urine tests during treatment and follow-up visits.

How Is the Trial Designed?

Group I: Single arm, open-label Experimental Treatment 1 Intervention

Belimumab 10 mg/kg once every 2 weeks for 3 doses, and then once every 4 weeks for 5 doses, delivered via 1-hour intravenous (IV) infusion.

Belimumab is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as Benlysta for:

• Systemic lupus erythematosus (SLE)

Approved in European Union as Benlysta for:

• Systemic lupus erythematosus (SLE)

Approved in Canada as Benlysta for:

• Systemic lupus erythematosus (SLE)

Approved in Japan as Benlysta for:

• Systemic lupus erythematosus (SLE)

Who Is Running the Clinical Trial?

National Institute of Allergy and Infectious Diseases (NIAID)

Lead Sponsor

Trials

3,361

Recruited

5,516,000+

Published Research Related to This Trial

Belimumab is a monoclonal antibody that effectively targets and inhibits B-cell activating factor, leading to reduced B-cell levels and improved disease activity in patients with active systemic lupus erythematosus (SLE).

Clinical trials and post-marketing data indicate that belimumab is beneficial for lupus patients who continue to experience active disease despite receiving standard of care therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Post-marketing experiences with belimumab in the treatment of SLE patients. Askanase, AD., Yazdany, J., Molta, CT.[2015]

Belimumab (Benlysta®) is an effective treatment for adults with active, autoantibody-positive systemic lupus erythematosus (SLE), particularly for those who have high disease activity despite standard therapy.

In multinational trials, patients receiving belimumab showed significantly higher rates of achieving an SLE Responder Index response at 52 weeks compared to those receiving a placebo.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Belimumab: a guide to its use in systemic lupus erythematosus. Scott, LJ., Burness, CB., McCormack, PL.[2016]

In a study of 14 SLE patients treated with belimumab, significant reductions in total B cells, especially naive and transitional B cells, were observed after 6 months, correlating with decreased serum BLyS levels.

The reduction in total B cells within the first 6 months of therapy was significantly associated with improved disease activity (SLEDAI-2K) at 12 months, suggesting that monitoring B cell changes could help predict treatment response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Association Between Changes in BLyS Levels and the Composition of B and T Cell Compartments in Patients With Refractory Systemic Lupus Erythematosus Treated With Belimumab. Regola, F., Piantoni, S., Lowin, T., et al.[2020]

In a study of 17 female patients with lupus nephritis treated with belimumab for a median of 36 months, all patients experienced resolution of arthralgia and skin manifestations, indicating its efficacy in managing these symptoms.

Belimumab treatment led to normalization of proteinuria in three patients and allowed for the reduction or complete withdrawal of corticosteroids in 35% of patients, demonstrating its potential to improve kidney function and reduce reliance on steroids.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Belimumab may decrease flare rate and allow glucocorticoid withdrawal in lupus nephritis (including dialysis and transplanted patient). Binda, V., Trezzi, B., Del Papa, N., et al.[2021]

Belimumab, a targeted B-lymphocyte stimulator inhibitor, has shown significant efficacy in treating systemic lupus erythematosus (SLE) in late-stage clinical trials, particularly when combined with standard care, demonstrating statistically significant improvements over placebo.

The treatment has been well tolerated, with discontinuation rates and adverse events comparable to those of placebo, suggesting a favorable safety profile as it moves towards potential FDA approval.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Belimumab: a BLyS-specific inhibitor for systemic lupus erythematosus. Wiglesworth, AK., Ennis, KM., Kockler, DR.[2013]

Benlysta (belimumab) is the first new drug approved for systemic lupus erythematosus (SLE) in 50 years, providing a new treatment option for patients with this complex disease.

Clinical trials suggest that Benlysta is effective in reducing SLE activity and flares in patients who are antinuclear antibody-positive, potentially allowing for lower doses of background medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Belimumab and the clinical data. Shum, K., Askanase, A.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3465857/

Effects of belimumab, a B lymphocyte stimulator-specific ... Belimumab treatment improved overall SLE disease activity in the most common musculoskeletal and mucocutaneous organ domains.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9314515/

Real-World Effectiveness of Belimumab in Systemic Lupus ... In randomized clinical trials, belimumab was found to reduce the incidence and severity of flares; in BLISS-52, the risk of flare was significantly reduced and ...

3. lupus.bmj.com lupus.bmj.com/content/11/1/e001111

Evaluating the real-world effectiveness of belimumab in ... After 6 months, 52.3% and 55.3% of patients had achieved MID in RAPID3 and PPI, respectively. Outcome measure trajectories indicated improved ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S0003496724009610

A pivotal phase III, randomised, placebo-controlled study of ... The total rate of immunogenic response (a positive anti-belimumab antibody result) was low (placebo 14/235 (6.0%); belimumab 1/470 (0.2%)).

5. bmcpregnancychildbirth.biomedcentral.com bmcpregnancychildbirth.biomedcentral.com/articles/10.1186/s12884-025-07600-5

Role of belimumab in recurrent spontaneous abortions ... The findings suggest that belimumab is both safe and effective for treating RSA with lymphocyte dysfunction, indicating its potential as a therapeutic strategy ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3389390/

Efficacy and Safety Data of Belimumab in Patients with ... Total numbers of circulating B cells were decreased 20–25% over the 1-year treatment periods in the respective trials, with no observed decreases in CD4 and CD8 ...

7. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2025/125370s085lbl.pdf

BENLYSTA (belimumab) for injection, for intravenous use ... Available data do not support the safety and efficacy of concomitant use of BENLYSTA with rituximab in patients with SLE. An increased incidence of serious ...

8. jrheum.org jrheum.org/content/41/2/300

Disease Control and Safety of Belimumab Plus Standard ... Disease control and safety profile were maintained in patients with active SLE taking belimumab plus standard therapy for up to 7 years.

9. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC2592791/

Biologic activity and safety of belimumab, a neutralizing anti-B ... Belimumab was well tolerated and reduced peripheral B-cell levels in SLE patients. These data support further studies of belimumab in autoimmune disorders.

10. benlystahcp.com benlystahcp.com/lupus/mechanism-of-action/

Lupus Mechanism of Action | BENLYSTA (belimumab) for HCPs BENLYSTA is the only FDA-approved treatment designed to target BLyS/BAFF, an underlying cause of lupus and lupus nephritis.